The Effect of Diltiazem on Propranolol Absorption Using in Situ Single Pass Intestinal Perfusion Technique in Rats

Fayyad, Hanan (2017) The Effect of Diltiazem on Propranolol Absorption Using in Situ Single Pass Intestinal Perfusion Technique in Rats. Masters thesis, Al Azhar University Gaza.

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Abstract

Title: The Effect of Diltiazem on Propranolol Absorption Using in situ Single Pass Intestinal Perfusion Technique in Rats. Introduction: Propranolol HCl is a synthetic non selective β-adrenergic receptor-blocking agent. Regarding its pharmacokinetic behavior propranolol HCl has almost complete and rapid absorption from gastrointestinal tract; however, its bioavailability is approximately 25% after oral administration. Propranolol HCl is a substrate for a distributed P-glycoprotein along intestine that can secrete it back into intestinal lumen. Aim: To investigate the influence of diltiazem HCl as P-glycoprotein (P-gp) inhibitor on the level of intestinal absorption of propranolol HCl, namely on absorption rate constant (ka). Methodology: Single Pass Intestinal Perfusion (SPIP) technique in rats was conducted on three groups of Wistar albino rats (n=6 per group). The first group was perfused with propranolol HCl (75 μg/mL) alone, while the second and the third group were perfused with propranolol HCl (75μg/m/) and diltiazem HCL (250 μg/mL) and (1000 μg/mL) respectively. Whole small intestinal segment of anaesthetized rats were cannulated and perfused by propranolol HCl in normal saline at 37 °C in absence and presence of diltiazem HCl in perfusion solution. Samples were obtained from outlet tubing at different time intervals, propranolol HCl remnant concentration assayed using UV-spectrophotometric method, and the absorption rate constant (ka) values of the drug were calculated. Results: The absorption rate constant (ka) value of propranolol HCL in the absence of diltiazem HCl was 0.810 ± 0.014 hr-1. The absorption rate constant ka values of propranolol HCL in the presence of diltiazem HCl (250 μg/mL and 1000 μg/mL) were 0.778 ± 0.012 hr-1 and 0.857±0.030 hr-1, respectively. No significant difference in ka values of propranolol HCl was observed when the drug has been co-perfused with P-gp inhibitor (diltiazem HCl) at two different concentrations level (P>0.05). IV Conclusion: The probable explanation for the null effect of P-gp inhibitor on propranolol ka is that P-gp plays a minimal role in the in situ intestinal absorption process of propranolol with high water solubility and high membrane permeability. Keywords: Absorption Rate Constant (ka), Diltiazem HCl, Efflux, P-glycoprotein (P-gp), Pharmacokinetics, Propranolol HCl, Single-Pass Intestinal Perfusion technique (SPIP).

Item Type: Thesis (Masters)
Subjects: Q Science > Q Science (General)
Depositing User: أ. طارق زياد عبد حنونة
Date Deposited: 18 Aug 2020 08:36
Last Modified: 18 Aug 2020 08:36
URI: http://scholar.alaqsa.edu.ps/id/eprint/2002

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